Viruses bind tightly to specific cell surface macromolecules as the first step in infection of a cell. This highly specific interaction may be an appropriate target for anti-viral drugs. New information on virus receptors now makes it feasible to develop and test receptor-specific drugs for murine and human coronaviruses. We recently identified a 110K glycoprotein receptor for the murine coronavirus MHV on cell membranes from MHV- susceptible Balb/c mice, which is absent from membranes of MHV-resistant SJL/J mice. We propose to use our newly developed anti-receptor antibodies to identify the Balb/c gene that encodes the MHV-receptor. This gene will be cloned and sequenced to determine the characteristics of the MHV-receptor. The functional domain of the receptor will be identified. In in vivo and in vitro models for coronavirus infection, we will attempt to interfere with virus attachment to cells using synthetic peptides mimicking the receptor-binding domain of the virus attachment protein or the virus-binding domain of the receptor, or using monoclonal and or anti-idiotype antibodies directed against the receptor- or virus-binding sites. With the MHV system, we can test effectiveness of receptor-specific drugs both in local respiratory infections and in systemic and central nervous system infections. Using the MHV system as a model, we will identify, clone and sequence a receptor for human coronaviruses, which cause about 20% of viral respiratory infections in man. We will develop antibodies and/or synthetic peptides which interfere with human coronavirus-receptor interactions in vitro. These studies focus on the great specificity and high affinity of the virus-receptor interaction as a target for development of antiviral drugs.